Next-generation therapy of carcinomas driven by neuregulins and oncogenic tyrosine kinases will be addressed by this group through:

(i) Genome-wide screening for mechanisms that negatively regulate signal transduction. The feasibility of harnessing the identified mechanisms for therapy will be examined.

(ii) Elucidation of modulators of ErbB-2/HER2 stability using systematic loss of function analysis and automated fluorescent readouts.

(iii) Establishment of diagnostic tools for patient-tailored therapy based on genomic sequences of neuregulins and expression profiles.

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• Katz, M., Shtiegman, K., Tal-Or, P., Yakir, L., Mosesson, Y., Harari, D., Machluf, Y., Asao, H., Jovin, T., Sugamura, K., and Yarden, Y. (2002). Ligand-Independent Degradation of Epidermal Growth Factor Receptor Involves Receptor Ubiquitylation and Hgs, an Adaptor Whose Ubiquitin-Interacting Motif Targets Ubiquitylation by Nedd4, Traffic 3, 740-751.
• Oved, S., and Yarden, Y. (2002). Signal transduction: molecular ticket to enter cells, Nature 416, 133-6.
• Waterman, H., and Yarden, Y. (2001). Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases, FEBS Lett 490, 142-52.
• Yarden, Y., and Sliwkowski, M. X. (2001). Untangling the ErbB signalling network, Nat Rev Mol Cell Biol 2, 127-37